Integrating HIV/AIDS and Alcohol Research

KENDALL J. BRYANT, PH.D., is coordinator for Alcohol and HIV/AIDS Research at the National Institute on
Alcohol Abuse and Alcoholism, Bethesda, Maryland.

STEVE NELSON, M.D., is dean of the Louisiana State University Health Sciences Center School of
Medicine, New Orleans, Louisiana.

R. SCOTT
BRAITHWAITE, M.D., is chief of the Section of Value and Comparative Effectiveness and director of
The Operations Research Collaboration for Health (T.O.R.C.H.) in the Division
of General Internal Medicine, both at the New York University School of
Medicine, New York, New York.

DEIDRA ROACH, M.D., is a medical officer in the Office of Collaborative Research at the National
Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland.

Many people at risk for or already infected with HIV abuse alcohol,
contributing to the difficulties in preventing the spread of the infection and
treating infected patients. Thus, alcohol-abusing patients may delay testing
for HIV, accessing appropriate medical care, and initiating antiretroviral
therapy (ART), which may hasten disease progression to full-blown AIDS. Alcohol
abuse also increases the risk of HIV infection by promoting risky behaviors and
counteracting efforts to minimize the risk of infection, prevent transmission
of the virus to others once exposure has occurred, and reduce the risk of
progression and organ or tissue injury after infection. In HIV-infected people
undergoing treatment, concurrent alcohol abuse often renders treatment
ineffective because patients frequently fail to adhere to the strict treatment
regimens necessary to achieve control of the infection. Moreover, alcohol may
interact with ART medications and exacerbate adverse effects of these
medications. Future research needs to better integrate behavioral and
biological research to identify strategies to prevent the spread of HIV infection
in alcohol-abusing populations as well as focus on translational research to
effectively implement promising approaches on a large scale. Key words: Alcohol consumption; alcohol abuse; alcohol and other drug effects and
consequences; risk factors; risky sexual behavior; human immunodeficiency
virus; acquired immune deficiency syndrome

The acquired immune deficiency
syndrome (AIDS) was first recognized in 1981; subsequently, researchers
determined that it was caused by infection with the human immunodeficiency
virus (HIV). Since then, the disease has become a pandemic, with the virus
infecting almost 60 million people worldwide, killing 25 million of them (Doran
2009). Although researchers have learned much about the nature
of the virus, the course of the disease, the routes of transmission, and
strategies to suppress viral replication and disease progression, the epidemic
continues unabatedly, particularly in less developed countries. Even in the
United States, where many prevention campaigns have been implemented and
awareness of the transmission routes is relatively high, between 55,000 and
60,000 people become newly infected with HIV every year (Centers for Disease Control
and Prevention [CDC] 2008a). With improved
treatment options, HIV infection in the United States and other Western
countries has evolved from an acute illness with rapid progression and death to
a chronic condition with, in many cases, a life expectancy of 20 to 40 years,
thanks to the knowledge gained from research. Globally, however, approximately
2 million people died from the disease in 2008 (Doran 2009).

Nevertheless, many challenges remain in preventing both infection
with the virus and progression of the disease. One of the many factors
contributing to the difficulties of preventing the spread of the infection and treating infected patients is the
acute or chronic alcohol use of people who are at risk for infection or who already
are infected. The alcohol–HIV/ AIDS literature has grown extensively over
the past 15 years, and a variety of recent reviews of this literature have
summarized the interactions of alcohol use and HIV/AIDS in behavioral,
biological, and biomedical areas (e.g., Bryant 2006; Van Thieu and Koblin
2009). This attention to the effects of alcohol consumption and mechanisms of
impairment reflects
an increasing desire to fully address
a broader scope of the epidemic in strategic ways.

A plethora of studies has demonstrated that alcohol use can impact
the risk and consequences of HIV infection on a variety of levels. For example,
both acute and chronic alcohol use, as well as the venues where people consume
alcohol, can increase the likelihood of risky sexual behavior, thereby
influencing the incidence of infection. After infection has occurred, alcohol
use may hasten the progression of the disease to full-blown AIDS, for example,
because alcohol-abusing patients may delay testing for infection, accessing
appropriate medical care, and initiating antiretroviral therapy (ART). All of
these factors can amplify the risk that the infection goes untreated and that
other people are infected. Furthermore, chronic alcohol use and the presence of
alcohol use disorders (i.e., alcohol abuse or dependence) also contribute to
various comorbid conditions (e.g., liver disease, other co-occurring
infections, or cognitive dysfunction) that have an impact on the progression of
the HIV infection. Finally, alcohol interacts with many of the medications used
to treat HIV infection/AIDS, and chronic alcohol use impairs patients’
adherence to ART regimens, thereby contributing to greater morbidity and mortality
among the affected patients. In fact, studies found that even nonhazardous alcohol
use (i.e., less than five standard drinks per drinking day) once a week or more
can reduce survival of HIV-infected people by 1 year, and daily hazardous use
(i.e., five or more standard drinks per day) reduces survival by 6.4 years
(Braithwaite et al. 2007). To date, however, HIV/AIDS prevention and treatment
strategies do not adequately take into consideration patients’ drinking
behaviors. Moreover, prevention specialists and health care providers dealing
with alcohol-consuming patients at risk of or already infected with HIV need
additional information in order to implement effective interventions in both
uninfected (i.e., HIV-negative) and infected (i.e., HIV-positive) populations.

This issue of Alcohol
Research & Health looks at the alcohol–HIV/AIDS interaction
from a variety of angles, addressing prevention issues, the physiological
effects of alcohol–HIV/AIDS comorbidity, as well as treatment
implications. As an introduction, this article will provide a brief overview of
these topics; for more in-depth information, the reader is referred to the
subsequent articles. In addition, this article highlights some suggestions for
future research directions that may be able to shed more light on the
underlying behavioral and biological processes in at-risk and HIV-infected
individuals and will thereby help in the development of more effective
prevention and treatment approaches.

Only through the development of an integrative and translational
framework for HIV/AIDS and alcohol research can the devastating consequences of
the HIV/AIDS epidemic be ameliorated in the future. Such a framework is
presented here, which—although by no means complete—can illustrate
the complexity of the interactions of alcohol use and alcohol-related
behaviors with overall exposure and susceptibility to HIV infection. This
framework represents an adaptation of an operations research model for HIV
infection, transmission, and progression developed by Dr. Scott Braithwaite and
his colleagues (pp. 280–287 in this issue). The primary aim of that model
is to examine and compare the contributions of individual, group, and
social–structural factors in increasing exposure and susceptibility to
HIV infection and to compare the effects of interventions targeting one or more
of these factors. This work extends and integrates analyses that look at simple
relationships between alcohol use and sexual risk behavior to a “systems”
multifactorial approach.

SCOPE OF THE HIV/AIDS EPIDEMIC

The population primarily affected by HIV infection and AIDS
has changed since the beginning of the epidemic. According to the U.S. Surgeon
General, “the epidemic has evolved from one centered on white gay men to one
increasingly impacting people of color, women, and the young” (Shelton 2000, p.
1). Particularly worrisome is the increase in the number of women infected by
HIV and the number who go on to develop AIDS. For example, in the United
States, the proportion of women among newly reported AIDS cases increased from
7 percent in 1985 to 25 percent in 2000 (National Institute on Allergy and
Infectious Diseases [NIAID] Fact Sheet HIV/AIDS 2002) and 27 percent in 2005
(CDC 2008b). Thus, in 2005,
almost 96,000 women were living with AIDS in the United States, representing 23
percent of all AIDS cases that year (CDC 2008b).
Particularly, non-White women now are disproportionately affected. Thus, whereas
African-American and Hispanic women together represent approximately 24 percent
of all U.S. women, they accounted for more than 82 percent of AIDS diagnoses
for women reported in 2005 (CDC 2008b).
Moreover, HIV/AIDS now is associated with high mortality among women, coming
only behind deaths from cancer or heart disease. Thus, in 2004 it was the fifth
leading cause of death among all women ages 35–44 years and the sixth
leading cause of death among all women ages 25–34 years. These numbers
are comparable with those found in men of the same age-groups. In Black women,
the situation was even more dramatic, with HIV/AIDS being the leading cause of
death among Black women ages 25–34 (compared with fourth leading cause
among men of that age-group) and the third leading cause of death among Black
women ages 35–44 (second leading cause in men of that age-group) in 2004
(CDC 2008b).

These
numbers underscore the need to understand the evolving
epidemic, particularly among women and minority groups, in order to develop
sustainable prevention and intervention approaches. For example, the fact that
more women become infected, particularly women of childbearing age, implies
that the risk of mothers transmitting the disease to their children before,
during, and after birth also increases, which necessitates appropriate
prevention and treatment approaches. Additional facts about the HIV/AIDS
epidemic that need to be considered when developing strategies to prevent
further infections and treat existing patients both in the United States and
worldwide are listed in the table.

Table: Facts About the HIV/AIDS Epidemic in the United States and Worldwide

United States

Roughly 1 million people were living with HIV/AIDS in the United States at the
end of 2003 (CDC 2008c).

Since the start of the AIDS epidemic, 1.5 million Americans have been infected
with HIV and more than 524,000 have died of AIDS.

In 2006, the number of new HIV infections in the United States was
approximately 56,300 (CDC 2008a).

Worldwide, more than 15 million children have lost one or both parents to AIDS;
this number is expected to increase to 20 million by 2010 (Global AIDS Alliance
2009).

Impact of Alcohol Use on the HIV/AIDS Epidemic

Alcohol use is common in all
population subgroups in the United States, and data show that 4.4 percent of
American adults meet the criteria of alcohol dependence (Grant et al. 2004). In
addition, as many as 35 percent of adult drinkers may experience mild to
moderate problems related to alcohol without physical dependence and therefore
may be considered problem drinkers. Many of these drinkers are at risk for HIV
infection, are in the early stages of infection without their knowledge and
have not sought treatment but continue to drink, or have received a diagnosis
of HIV/AIDS and have begun treatment with varying success. Studies also
identified a strong association among women between alcohol and other drug
abuse and acquisition and progression of HIV/AIDS. Thus, studies sponsored by
NIAID found that in the United States, alcohol use, history of childhood sexual
abuse,
current domestic abuse, and use of crack/cocaine all are associated with an
increased risk of heterosexual transmission of HIV (NIAID 2004). To date, however,
no systematic estimates of alcohol use, abuse, and dependence using a variety
of sensitive measures have been carried out in at-risk or infected populations.
In an analysis of an HIV treatment population in the Veteran’s Aging Cohort
Study in the United States, 35 percent of the patients were classified as
currently or previously alcohol dependent (Justice et al. 2006). In Kenya, a
study of people participating in a voluntary counseling and testing program
(who can be considered at risk of HIV infection or may be infected) determined
that more than 60 percent of the current drinkers could be classified as
hazardous drinkers (Mackenzie et al. 2008). The article by Scribner and
colleagues (pp. 179–183, in this issue) summarizes the existing
information on the epidemiology of HIV/AIDS, including alcohol use patterns in
the affected population subgroups. However, a better understanding of alcohol
use patterns in at-risk and infected populations clearly is needed to more
accurately define the scope of the problem and evaluate the consequences of
alcohol use in these populations.

Rehm and colleagues (2009) recently related alcohol consumption to
the global burden of disease and injury. The analyses demonstrated, for
example, that alcohol consumption increases the risk for contracting infectious
diseases, including tuberculosis (TB) and HIV/AIDS, as well as exacerbates the
consequences of these diseases, such as more rapid progression, development of
multidrug-resistant forms, and premature mortality from failed treatment. In
absolute terms, alcohol use accounts for 13.5 percent of global mortality from
infectious diseases, with the largest impact found in low-income countries with
elevated rates of alcohol consumption, such as South Africa. Overall, alcohol
use can contribute to HIV/AIDS deaths directly or indirectly—for example,
through alcohol-related unintentional and intentional injuries, cardiovascular or
hepatic damage, or neuropsychiatric disorders. These consequences of excessive
alcohol use have not been assessed adequately in HIV-positive populations. Some
analyses of cohorts of HIV-infected patients indicate that the role of
alcohol-related hepatic and cardiovascular effects in HIV/AIDS progression and
death are underappreciated and need to be addressed systematically (e.g.,
Conigliaro et al. 2003; also see the article by Freiberg and colleagues, pp.
237–246, in this issue). Clearly, research addressing the role of both
direct and indirect alcohol effects needs to be developed further.

IMPACT OF ALCOHOL USE ON HIV/AIDS PREVENTION

Alcohol consumption is prevalent in nearly every population
group at high risk for HIV infection. In all of these groups, alcohol use can
affect the risk of infection and the effectiveness of prevention efforts as
well as exacerbate the consequences of an infection and progress of the
disease. There are several ways to look at strategies to prevent these alcohol
effects. One way is to compare behavioral prevention efforts (e.g., reduction
of risky sexual behavior) and biomedical prevention efforts (e.g., vaccination
or prophylactic treatment) and evaluate alcohol’s impact
on both areas. A second way is to look at alcohol’s contribution at different
stages of the patient’s infection process (i.e., risk of exposure to the virus,
risk of infection once exposure occurs, and risk of HIV progression and organ
damage once infection occurs). The following sections discuss both of these
perspectives.

Influence on Behavioral Versus Biomedical Prevention Strategies

Influence on Behavioral Prevention Strategies. Alcohol use may increase people’s likelihood
of risky behavior and undermine the effectiveness of many prevention efforts
through a variety of pathways:

Alcohol
has a direct impact on risk behaviors by impairing judgment and cognition and
by disinhibiting behavior, thereby potentially increasing the likelihood of
unprotected sex and other risky behaviors. In addition, alcohol-related outcome
expectancies, perceived social norms, and other beliefs can influence behavior
more indirectly.

People who
drink frequently also use other drugs that may enhance the risk of direct
exposure to HIV, for example, by injection drug use.

Alcohol
consumption frequently occurs in settings (e.g., bars, clubs, and informal
drinking places) where unprotected sex with several partners is likely to occur
(Kalichman
et al. 2007b). In general,
drinking (particularly heavy drinking) is associated with risky sexual
behaviors. For example, one study (Mackenzie and Kiragu 2007) reported that in
a Kenyan sample, current drinkers were four times more likely to have multiple
sexual partners than nondrinkers. Other studies found that alcohol-serving
establishments often also are the places where sex partners meet, resulting in
the formation of “sexual networks” in which HIV can spread rapidly (Chersich
and Rees 2010; Weir et al. 2003). Finally, alcohol dependence may lead to
trading sex for drinks, as has been reported in South Africa (see Kalichman et
al. 2007a)

Alcohol
(like other drugs) often is a tool of sexual coercion, resulting in increased
risk of HIV infection. For example, Stockman and colleagues (2009) reported
that women who had been sexually coerced by use of alcohol and other drugs had
a 1.5 times higher risk of having multiple sex partners than women who had not
been coerced using drugs.

Based on the knowledge of these pathways, researchers have
developed numerous prevention measures targeted at high-risk groups (e.g., men
who have sex with men, injection drug users, or victims of sexual coercion) or
high-risk settings. The article by Kalichman (pp. 184–194, in this issue)
describes some of these behavioral interventions and the evidence for their
effectiveness.

It is important to note, however, that despite the known effects of
alcohol use on HIV transmission risk, alcohol use commonly is treated only as a
background characteristic in HIV prevention measures, so that many behavioral
HIV prevention interventions targeting people who drink do not seriously
address alcohol use as a risk factor, thereby potentially reducing intervention
effectiveness. Indeed, there are numerous examples where drinking may have
reduced the potential benefits of an intervention or confounded interpretation
of the results (e.g., Carey et al. 2010). Consistent with these findings,
studies that have examined alcohol use as a moderator of HIV risk behavior outcomes
have suggested that risk reduction interventions are more effective for participants
who do not drink heavily compared with participants who report heavy drinking
(e.g., Kalichman et al. 2008). Thus, future studies need to pay greater
attention to the role of alcohol as a contributor to HIV transmission risk when
designing and testing new prevention approaches.

Influence on Biomedical Prevention Strategies. Alcohol use not only may
interfere with behavioral prevention approaches but also may threaten
the success of emerging biomedical approaches to HIV prevention. One such
approach is vaccination, and many researchers are looking for an HIV vaccine.
Should such a vaccine prove effective, however, alcohol use may interfere with
the person’s immunological response to the vaccination.
A similar effect of alcohol abuse already has been reported in response to
vaccination against the hepatitis B virus (HBV) (Hagedorn et al. 2010).
Moreover, drinkers often are less connected to the health care system and therefore
may be less likely to initiate vaccination.

The success of other biomedical approaches to HIV prevention, such
as pre- and postexposure prophylaxis, microbicides, and others, also may
be hampered by alcohol use because these approaches require proper product application
and medication adherence. Recent research has demonstrated that alcohol use
interferes with reliable adherence to antiretroviral medication regimens
(Braithwaite et al. 2005; Glass et al. 2010; Hendershot et al. 2009), so it is
likely that similar effects occur with other biomedical prevention strategies
that require strict adherence, such as prophylactic treatment with HIV
medications, test and treat,1 [1The term
test and treat refers to a strategy whereby people are aggressively tested for
HIV infection and are started on antiretroviral medications as soon as they
test positive for the virus, with the goal of reducing the amount of virus in
the blood and thereby preventing transmission of the infection to others. To
date, many people do not know they are infected because they are not regularly
tested, and antiretroviral medications typically are started only once the
patient begins to exhibit more severe symptoms of the infection.] or microbicides. Alcohol’s interference
with biomedical HIV prevention strategies is discussed in more detail in the
article by Mayer and colleagues (pp. 195–202, in this issue), but it
appears likely that alcohol use can reduce the effectiveness of all of these
approaches. Nevertheless, current initiatives for evaluating the test-and-treat
approach have not integrated behavioral interventions to address alcohol use
and its relationship to nonadherence (Dieffenbach and Fauci 2009). Continuing
to ignore the influence of alcohol use
on response to behavioral prevention strategies as well as on adherence,
however, will reduce the potential
of any HIV prevention intervention.

Influence on Prevention
at Different Stages of the
Infection Process

Reducing Risk of Exposure. Reducing people’s risk of
being exposed to HIV infection obviously is important for stemming the HIV/AIDS
epidemic in the United States and internationally. One approach to achieving
this is using ecological models that synthesize the influences of a variety of factors
underlying exposure to people with active HIV infection, particularly if they
represent the interactions between these factors and alcohol use. Among the
factors to be considered are the following (see figure 1 in the sidebar):

Social network
characteristics that include factors such as the number of partners,
concurrency of alcohol and other drug use and sexual relationship, and age
symmetry within a relationship, where an older HIV-positive partner may
influence the risk behavior of the younger partner. All of these
characteristics establish or change social norms (for a more detailed
discussion, see Latkin et al. 2009).

Demographic characteristics that interact with these social network characteristics and may be used to
classify individuals in terms of their overall susceptibility to infection as
well as their group identity (e.g., minority women, young Black men).

Psychosocial characteristics that may influence drinking behaviors by altering expectations for engaging
in risk behaviors, contributing to psychosocial disinhibition, and influencing
settings and situations for alcohol use and risk behaviors.

Biological factors,
such as hormonal, neurological, and other characteristics, that also can impact
risk of exposure.

Among these, social network characteristics are of particular
interest because models representing social networks can help discover specific
risk patterns and suggest targeted interventions. Such models may capture
complex interactions between such diverse factors as alcohol levels over time
in a specific geographic environment (determined using spatial mapping of
specific alcohol-related venues), sex and alcohol or other drug use (using
social network mapping), and individual-level characteristics. The article by
Scribner and colleagues (pp. 179–183, in this issue) describes the
development of such ecological models in more detail.

To interfere with this complex range of influences and thus reduce
risk of exposure, interventions at multiple levels may be necessary. These may
include structural interventions at the economic and policy levels, such as
microeconomic interventions for women in underresourced countries that allow
the women to generate sufficient income so they
do not have to work as sex workers. Other interventions may be tailored to
specific settings, including both formal (i.e., bars and nightclubs) and
informal (i.e., “shebeens” or corner gathering places for adolescent drinking)
settings in which alcohol consumption occurs and that may provide a source of
employment, profit, and socializing. Of particular concern here are settings
that facilitate mixing of higher-risk and lower-risk populations (e.g.,
cross-border settings where truck drivers rest). Interventions that have been
used in these diverse settings are described in the article by Kalichman (pp.
184–194, in this issue).

Reducing Risk of Transmission/Infection Given
Exposure. Not all people who are
exposed to the virus actually become infected, and certain models are
evaluating how transmission risk can be reduced. Important behavioral
characteristics that augment the likelihood of infection and therefore are
important targets of prevention efforts include alcohol consumption, lack of
condom use or other protection (e.g., microbicides), and behaviors that result
in untreated sexually
transmitted infections (STIs) (see figure 2 in the sidebar). Alcohol
consumption is a particularly important factor in this context because it may
affect behavioral mediators of transmission (e.g., likelihood of condom or
microbicide use) as well as nonbehavioral mediators (e.g., function of the
person’s immune system). Therefore, research on the impact of alcohol use
on the use and effectiveness of microbicides, vaccines, and preventive
therapeutics has great potential to inform interventions to reduce the risk of
infection. This is discussed in more detail in the article by Mayer and
colleagues (pp. 195–202, in this issue). Equally important is research on
the role of alcohol use in immune function impairment and in the effectiveness
of agents striving to reconstitute the immune function of tissues and organs
impacted by both alcohol and HIV/AIDS. In all cases, research on strategies
that also can be used in settings with limited resources is of particular
interest.

Another important area of study concerns approaches to reduce
transmission risk that have both a behavioral and a biological component, such
as prophylactic treatment with HIV medications. These medications are thought
to reduce the risk of transmission if taken before or after exposure to the
virus (“morning after” use). However, their use also has a behavioral component
because the success of this approach depends on the patient adhering to the
treatment regimen. The success of this pharmacological intervention still is
under investigation; particularly, there is as yet no information on how
drinkers will use this chemical prophylaxis approach. Because alcohol use is
known to reduce treatment adherence and because of beliefs about the
medications’ toxicity (i.e., some people report discontinuing these medications
when they go to a party), it is unlikely that prophylactic treatment will be
widely accepted by people with alcohol use disorders. However, because these
pharmacological interventions potentially are important tools for preventing an
infection in people exposed to HIV, they need to be investigated further in
different patient groups.

Reducing Risk of Progression and Organ/Tissue Injury. Once people are infected with HIV, alcohol use may impact progression of the
infection and other diseases through its effects on access to and effectiveness
of ART, interaction with viral characteristics, and contribution to organ and
tissue damage (see figure 3 in the sidebar). Alcohol use may impede access to
ART at several steps in the sequence of events that must occur for a person to
begin treatment:

Alcohol use may delay willingness to be tested for HIV, increasing the likelihood that
infection will only be detected after serious HIV-related disease develops.

Alcohol use may make it less likely that people with a diagnosed HIV infection link
with appropriate care and show up for regular appointments; these people
therefore are less likely to be considered suitable candidates for starting
ART.

Alcohol-abusing people may be less willing to start ART because of concerns over symptoms,
toxicity, or anticipated adherence problems.

All of these factors limit access to ART and therefore contribute
to the risk of HIV/AIDS progression and death.

SIDEBAR

MODEL FOR ALCOHOL
AND HIV/AIDS PREVENTION

Complex models are being developed
to describe the characteristics of the HIV epidemic and target
primary, secondary, and tertiary preventive interventions. Different stages of
HIV infection interact with alcohol use in different ways and represent
different key prevention issues. Mixtures of populations at risk for infection,
early in infection (and often unaware of their status), and those managing HIV
and co-occurring diseases change the focus for prevention activities. Current
prevention models that do not include alcohol use as an environmental, social,
group, and individual factor are limited in their representation of critical
outcomes for the three-stage model presented here.

Figure 1. General and specific risk
factors for infection. Multiple factors influenced by the use of alcohol
increase the risk for HIV infection. These factors interact to increase both
the general and specific contexts for infection events. Social networks, as
well as demographic, psychosocial, and biological characteristics are general
factors often used to target preventive interventions among alcohol users.
However, these categories and “compartments” interact to influence mediators of
increasing risk at the social level, such as social norms and economic inducers
of HIV risk and individual-level factors related to disinhibition and
biological susceptibility for infection. Scribner and colleagues (pp.
179–183, in this issue) and Kalichman (pp. 184–194, in this issue)
describe the importance of these multilevel models for prevention.

Figure 2. Early infection and transmission. The probability
of HIV infection in any contact event is influenced by individual behavioral
characteristics, such as alcohol use, the presence of other sexually transmitted
infections, and condom-use behaviors. These factors influence the frequency of
sexual contact with individuals of unknown HIV status and exposure to HIV. The
probability of transmission may be influenced by existing and future prevention
activities, such as pre-exposure prophylaxis, circumcision, or availability of
vaccines. Individual behavioral and host immunological response impact
transmission modulators when HIV is present. These include facilitators and
attenuators in specific encounters. These factors are discussed by Pandrea and
colleagues (pp. 203–218, in this issue) and future interventions by Mayer
and colleagues (pp. 195–202, in this issue).

Figure 3. Progression and mortality. After infection,
multiple factors influence organ and tissue damage and risk of mortality from
both HIV and non-HIV progression and interaction. These factors include patient
behavioral and biological characteristics related to treatment seeking and
adherence to effective medication regimens for multiple diseases. The effective
treatment for HIV/AIDS has extended patient survival, and other co-occurring
chronic diseases influenced by patterns of alcohol use often are the cause of
death. The special section in this volume (pp. 219–257) illustrates the
potential synergistic role of alcohol for liver, lung, cardiovascular, and
neurological injury and the role of adherence to complex treatment regimens in
treatment management over the life course.

END OF SIDEBAR

In addition to these effects on ART and its effectiveness, alcohol
abuse also has been shown to accelerate and magnify the organ and tissue damage
resulting from the HIV infection and from comorbid diseases. Some of
the acute and chronic interactions
of alcohol with HIV/AIDS progression and associated conditions are reviewed in
more detail in the article by Pandrea and colleagues (pp. 203– 218, in
this issue). Because the life expectancy of HIV-infected people has been
prolonged as a result of ART, comorbid conditions, such as hepatic, pulmonary,
neurological, cardiovascular, and metabolic diseases; certain tumors; and other
clinical manifestations associated either with long-term HIV or prolonged ART,
have assumed greater importance as causes of morbidity and mortality in
HIV-positive people. Most of these conditions, but particularly liver disease
and neurological disorders, can be exacerbated by alcohol abuse and dependence.
For example, ART frequently has hepatotoxic effects; moreover, many HIV-positive
patients also are infected with hepatitis B and C viruses that also damage the
liver (Goedert et al. 2002). Chronic alcohol consumption also causes liver
injury and may therefore accelerate the development of serious liver disease in
patients coinfected with HIV and hepatitis viruses. Thus, understanding liver
disease progression in the context of HIV infection and alcohol abuse is
becoming an important issue in caring for these patients. For example, research
is needed on the response of alcohol-abusing HIV patients to treatment of liver
disease. These and other issues are reviewed in the article by Barve and
colleagues (pp. 229–236, in this issue).

Another area of growing concern among HIV-positive patients is
neurological injury. Both HIV infection and alcohol abuse have detrimental
effects on brain function, which are reviewed in the article by Rosenbloom and
colleagues (pp. 247–257, in this issue). Another common neurological
disorder is peripheral neuropathy. This typically painful and debilitating
condition, which is characterized by inflammation or degeneration of nerves
outside the brain and spinal cord, severely compromises quality
of life and productivity. It is found
in approximately 30 percent of HIV-infected patients and almost 100
percent of AIDS cases (Ferrari et al. 2006). Similarly, peripheral neuropathy
is the most common neurological complication in alcoholism (Diamond and Messing
1994). Although both HIV infection and alcohol abuse
can induce peripheral neuropathy,
they may do so through different mechanisms, and this issue requires further
investigation.

Research also is needed to characterize the synergistic
interactions of alcohol, HIV infection, and ART
in other body systems. For example, as described by Drs. Freiberg and Kraemer
(pp. 237–246, in this issue), these interactions can play a significant role
in the development of cardiovascular disease. Similarly, lung health also can
be impaired in alcohol-abusing HIV-infected patients, as explained in the
article by Quintero and Guidot (pp. 219–28, in this issue). Research that
will lead to a better understanding of the effects
of alcohol on various HIV-associated comorbidities is a high priority and may
be promoted by the emerging field of systems biology. In addition,
translational and clinical studies are needed to translate basic research
results into improved strategies for preventing and treating these
HIV-associated comorbidities and their consequences.

TREATMENT OF CONCURRENT HIV/AIDS AND ALCOHOL PROBLEMS

Treatment of patients with concurrent HIV/AIDS and alcohol
problems is complicated and often ineffective. As mentioned earlier and further
described in the article by Drs. Braithwaite and Bryant (pp. 280–287, in
this issue), alcohol-abusing patients exhibit reduced adherence to their
treatment regimens, which typically have to be followed exactly in order to be
most effective. Failure to adhere to the regimen enhances the likelihood that
the virus becomes resistant to the medications used and that HIV disease
progresses more rapidly. At the same time, alcohol can interact with the HIV
medications and may exacerbate the toxic effects associated with the long-term
use of some of these agents. Fear of this toxicity leads many patients to stop
taking their medications when they know they will be drinking or
discourage them from initiating treatment at all.

A second aspect of the comorbidity of HIV/AIDS and alcohol abuse or
dependence is whether alcoholism treatment should be initiated as part of the
HIV/AIDS intervention. Alcoholism therapy requires substantial investments of
time, effort, and expense also at the part of the patient, which may seem unreasonable
to patients with less severe drinking problems. In addition, it is conceivable
that patients may be afraid of stigmatization if they seek treatment for
problem drinking, whereas seeking treatment for a medical condition may be
considered more acceptable. Finally, many problem drinkers at early stages of
change may not think they have a drinking problem and therefore do not think
they require treatment. Thus, perceptions regarding the need for and usefulness
of treatment for problem drinking may keep many affected patients from seeking
treatment in the first place. Even if treatment is initiated, which typically
involves behavioral approaches, the effectiveness of these interventions often
is limited, as described in the article by Samet and Walley (pp. 267–279,
in this issue).

These considerations underscore the need to develop pharmacological
and low-threshold interventions,
particularly for patients who are not prepared to invest in formal alcohol
treatment or who need to seek treatment outside of the usual alcohol treatment settings
(e.g., in HIV/AIDS testing and treatment settings). Moreover, new approaches
are needed for effectively encouraging problem drinkers to initiate
treatment—for example, by modifying their perceptions of the
acceptability of their drinking as well as of the attractiveness of various
intervention options for people at risk of HIV infection, of unknown HIV
status, or with active HIV infection. Finally, medications for alcohol-abusing
and alcohol-dependent HIV-positive patients are needed that ideally impact
drinking behavior as well as improve the patient’s immune function and decrease
progression of the HIV infection. Chronic alcohol use is associated with
impairment of the immune system. Among other effects, alcohol impairs the
functioning of the exact cells that are the targets of HIV—cells called
CD4 T-lymphocytes and macrophages. Thus, it would be desirable to have medications
that inhibit the alcohol-mediated spread of the HIV infection among the CD4
T-lymphocytes and which at the same time address the underlying alcohol
disorder, thereby enhancing adherence to ART. In fact, such an effect has been
observed with the medication naltrexone, which is used in the treatment of
alcoholism (Wang et al. 2006). However, additional treatment options are
needed, and novel pharmacologic approaches to the treatment of disorders
affecting the immune system have been suggested (Tuluc et al. 2009).

FUTURE RESEARCH

Alcohol use is one of the most modifiable factors
contributing to the risk of HIV infection as well as to the progression of
HIV/AIDS. Past research has shown the importance of alcohol use and misuse in
the acquisition, progression, and transmission of HIV disease. Even low levels
of alcohol use in HIV-positive people may lead to accelerated disease
progression. Moreover, alcohol use that occurs in high-risk situations and
modifies risk-taking behavior is likely to lead to increased rates of
transmission. Accordingly, elucidation of the interaction between the
behavioral actions and biological processes by which alcohol contributes to
increased disease susceptibility and progression
is necessary for developing tailored interventions to be used with individuals,
groups, and environments where the risk for infection and transmission
is high. These interventions need to
act at multiple levels to ensure their effectiveness.

The complex and global nature
of unresolved questions surrounding the relationship between alcohol and
HIV/AIDS indicates the need for a multidisciplinary approach to research. Thus,
investigators representing a broad array of academic disciplines and engaged in
cross-cutting fields of science need to work together to design
hypotheses-driven studies that utilize rigorous methodologies from
epidemiological, basic, clinical, and behavioral research. In particular,
biomedical research that can lead to improved treatments for people with
co-occurring HIV/AIDS and alcohol use disorders needs to be strengthened. This
also can help prevent the spread of HIV/AIDS, particularly from mothers to
their children (i.e., vertical transmission), which is an increasing threat
because of the growing numbers of women with HIV disease.

Focus on Integrating Behavioral and Biological Research

One important focus of any alcohol–HIV research needs
to be the integration of basic biological and behavioral research in order to
address both the behavioral aspects contributing to the spread of HIV infection
(e.g., risky sexual behavior or reduced adherence to ART in drinkers) and the
biological factors exacerbating infection risk and disease progression (e.g.,
alcohol-related impairment of the immune system or damage to other organs and
tissues). These findings then need to be translated into effective prevention
and treatment strategies for people whose drinking places them at risk of
adverse HIV-related outcomes, such as increased susceptibility to infection,
more rapid disease progression, treatment complications, and increased
mortality. In particular, this research needs to assess and strive to improve
the overall impact of prevention and treatment interventions focusing on
alcohol misuse in the target populations because, as shown in the article by
Samet and Walley (pp. 267–279
in this issue), the effectiveness of such interventions so far still is
limited. Some investigators have proposed conceptual models that integrate
multiple concurrent epidemics (i.e., syndemic models) for the prevention and
treatment for HIV; however, these models still need to be developed further to
reflect the different states of knowledge of multiple factors at many levels of
analysis that currently still exist in the field. Nevertheless, such operations
research models can help to more systematically identify the most promising
starting points for developing and implementing effective interventions
in specific at-risk populations, thereby helping to optimize limited research
and intervention resources.

This research also needs to take into consideration the different
needs of patients in different countries. For example, in the United States one
focus of the research is on long-term treatment of HIV to prevent disease
progression and reduce the risk of transmission to other people by lowering the
viral load of patients. In underresourced countries, in contrast, treatment
availability is limited, and the emphasis needs to be placed on strategies to
prevent drinking and/or risky sexual behavior in the populations at highest
risk of HIV infection. Particularly in settings where resources for prevention
and treatment are highly limited, neglecting to address alcohol use (the most
common form of substance abuse in those settings) and its association with
acquisition of HIV as well as treatment failure can be a costly error in the
longer term.

Focus on Translational Research

The lack to date of attention to alcohol use as a mediating
factor results at least in part from deficiencies in translational
research—the gap between research on these interrelationships and
development of appropriate interventions on the one hand and the actual
implementation of prevention and treatment strategies in real-world settings on
the other hand. This gap is only now beginning to be addressed (Hirschhorn et
al. 2007). Translational research stresses the need for developing a research
context for implementing and disseminating effective interventions in
combination with one another. For example, models are needed to systematically
identify choice points for developing, testing, and disseminating effective
intervention strategies, in the process incorporating a wide range of factors
related to alcohol use. Such an effective translational research agenda also
requires a pool of qualified investigators, an academic culture that fosters
collaboration between clinical and basic science researchers, institutional
structures that support interdisciplinary programs, and appropriate
administrative and regulatory processes.

CONCLUSION

Despite 30 years of research, HIV/AIDS still is one of the
greatest health challenges worldwide and continues to
take an enormous toll both in terms
of human suffering and mortality and with respect to the associated economic
costs. Alcohol use and misuse continues to play an important role in the
acquisition, progression, and transmission of HIV. Therefore, in order to reduce
the number of new HIV cases and improve the prognosis of those already infected
with the virus, it is essential to bring the two fields of alcohol research and
HIV research together to allow for advances in both prevention and treatment.

The articles in this issue of Alcohol
Research & Health present specific findings from current research
into the interactions of alcohol use and HIV/AIDS, providing an overview of
behavioral and biomedical prevention approaches, the physiological consequences
of concurrent alcohol use and HIV infection on the body, and treatment
challenges and strategies to address both conditions. Some articles summarize
research and offer models from relatively broad problem areas, whereas others
focus on specific problems that to date have received little attention.
Together, the articles provide a foundation for a discussion of future research
and new directions in these areas. Although this journal issue can only
represent a few of the multiple approaches to the problems associated with
alcohol use and HIV/AIDS, it begins to sketch out the current way of thinking
about the relationship of alcohol use to the HIV epidemic both in the United
States and abroad.

Much has been learned about this relationship in the past three
decades. For example, it is now clear that it takes a combination of
medications to control the infection; similarly, it may take a such a “cocktail
approach” combining vaccines and behavioral interventions to prevent the
acquisition and transmission of HIV infections. The challenge for researchers
and clinicians now is to understand how to develop the optimal combination of
preventive and therapeutic measures that remain effective over time. Meeting
this challenge will require the development of broad models that incorporate
all relevant perspectives; this can only be achieved by intensive and
multidisciplinary collaboration between the alcohol and HIV/AIDS fields.